Previously, we found that extreme DHA deficiency where the brain DHA level decreased by 70% significantly worsened the recovery from TBI. It is well-established that when omega-3 fatty acid is deficient, brain DHA is replaced by its omega-6 counterpart docosapentaenoic acid (22:5n-6, DPAn-6). The extent of this reciprocal replacement is known to be more pronounced with the severity of the omega-3 depletion in the diet. Therefore, the extent of omega-3 deficiency can be estimated using the ratio between DHA and DPAn-6 as an index. During this period, we tested the effect of lowering the brain DHA level to the humanized tissue level on the recovery outcome. We have previously documented using postmortem human brain tissue samples that brain DHA deficiency is approximately 30-40% of the adequate level where DPAn-6 is less than 0.01% of DHA. Pregnant mice were fed either omega-3 fatty acid adequate or deficient diets from the 14th day of pregnancy through the lactation period. Offspring mice were continued on the same diet until 16 weeks of age. This dietary treatment reduced the brain DHA level by 30% in comparison to the adequate control group. Age and gender matched mice from adequate and deficient groups were subjected to the CCI procedure and the TBI-induced motor and cognitive deficits were evaluated. We found that the spontaneous motor function recovery from TBI evaluated by the rotarod and beam walk tests was significantly slower in the omega-3 deficient male mice compared to the adequate animals. The difference in spontaneous recovery between the two groups is statistically significant (p<0.05). In addition, the anxiety-like behavior evaluated by the open field test was significantly greater in the deficient group (p<0.05). Nevertheless, these moderately DHA-depleted animals recovered significantly better in comparison to the severely depleted group. The female mice on deficient diet also showed increased anxiety-like behavior in the open field test and increased motor deficits as observed in the beam walk test. These data suggest that individual differences in the brain DHA status may be a significant factor contributing to individual recovery outcome. More importantly, the difference in the recovery outcome between adequate and moderately deficient animals with humanized brain DHA levels suggests an opportunity to improve the recovery outcome in humans by increasing the brain DHA content. To address the involvement of DHA-metabolites in the improved functional recovery, we also characterized DHA metabolites formed after TBI. Using an HPLC-electrospray ionization (ESI)-MS/MS metabolite profiling method that we have previously developed, we determined the time course for the production of endogenous metabolites of AA and DHA including TXB2, PGE2, hydroxy derivatives of DHA and AA as well as anandamide and synaptamide. We found three distinctive time course profiles for bioactive lipid metabolites in the TBI-inflicted brains; steadily rising, early (1 h) and 24 h peaking groups. Significance of the distinctive time course of the metabolite formation is now under investigation to devise supplementation protocol to improve recovery outcome.